The induced RNA-binding protein, HuR, targets 3'-UTR region of IL-6 mRNA and enhances its stabilization in periodontitis.

RNA-binding proteins (RBPs) regulate mRNA stability by binding to the 3'-untranslated region (UTR) region of mRNA. Human antigen-R (HuR), one of the RBPs, is involved in the progression of diseases, such as rheumatoid arthritis, diabetes mellitus and some inflammatory diseases. Interleukin (IL)-6 is a major inflammatory cytokine regulated by HuR binding to mRNA. Periodontal disease (PD) is also an inflammatory disease caused by elevations in IL-6 following an infection by periodontopathogenic bacteria. The involvement of HuR in the progression of PD was assessed using in-vitro and in-vivo experiments. Immunohistochemistry of inflamed periodontal tissue showed strong staining of HuR in the epithelium and connective tissue. HuR mRNA and protein level was increased following stimulation with Porphyromonas gingivalis (Pg), one of the periodontopathogenic bacteria, lipopolysacchride (LPS)-derived from Pg (PgLPS) and tumour necrosis factor (TNF)-α in OBA-9, an immortalized human gingival epithelial cell. The luciferase activity of 3'-UTR of IL-6 mRNA was increased by TNF-α, Pg and PgLPS in OBA-9. Luciferase activity was also increased in HuR-over-expressing OBA-9 following a bacterial stimulation. Down-regulation of HuR by siRNA resulted in a decrease in mRNA expression and production of IL-6. In contrast, the over-expression of HuR increased IL-6 mRNA expression and production in OBA-9. The HuR inhibitor, quercetin, suppressed Pg-induced HuR mRNA expression and IL-6 production in OBA-9. An oral inoculation with quercetin also inhibited bone resorption in ligature-induced periodontitis model mice as a result of down-regulation of IL-6. These results show that HuR modulates inflammatory responses by regulating IL-6.

Cerebral primitive neuroectodermal tumor in an adult male. A case report.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) are very rare. Malignant tumors of the cerebrum in young individuals are composed predominantly of undifferentiated cells, with moderate differentiation along either neuronal or glial lines. To our knowledge, cerebral PNETs in adults are extraordinarily rare and have been reported in only 11 cases, with little cytologic documentation in the literature. The cytopathologic, immunohistochemical and ultrastructural features of cerebral PNET arising in an adult male are presented. CASE: A cystic tumor, on computed tomography and magnetic resonance imaging, arose from the left frontal lobe in a 39-year-old man and contained histopathologic features of PNET. Specimens obtained from surgery revealed the presence of an undifferentiated type of PNET with moderate neuronal and glial differentiation and mild characteristic findings of peripheral PNET. The cytologic and histologic specimens showed evidence of a scattered pattern of blastic and undifferentiated tumor cells and a neural arrangement with Homer-Wright-like rosettes. Immunohistochemically, the tumor cells were glial fibrillary acidic protein, neuron-specific enolase, synaptophysin and CD-99 positive and epithelial membrane antigen, S-100 protein and vimentin negative. Ultrastructurally, neither microtubular structures nor intermediate filaments, except neurosecretory granules, were found in the tumor cells. CONCLUSION: Both immunohistochemical and ultrastructural studies on cytologic and histologic slides were important for the diagnosis of PNET because of establishing not only undifferentiated tumor cells but also neural and glial differentiation.

Cytopathological observations in a 27-year-old female patient with endometrioid adenocarcinoma arising in the lower uterine segment of the uterus.

The determination of the malignancy of an endometrioid adenocarcinoma arising in the lower uterine segment (LUS) is difficult because of the high degree of differentiation of adenocarcinoma. The cytopathological and immunohistochemical features of endometrioid adenocarcinoma arising in the LUS of a young adult female are presented. The preoperative cytopathological examination of a 27-yr-old female could not enable an accurate diagnosis of malignancy. Hysterectomy specimens revealed the presence of an endometrioid-type adenocarcinoma with minimal atypia and myometrial invasion, which was located in the LUS. This tumor was consistent with a histological diagnosis of endometrioid minimal-deviation adenocarcinoma (MDA). Immunohistochemically, the tumor's glands were p53-, proliferating cell nuclear antigen-, and carcinoembryonic antigen-positive, and estrogen receptor-, progesterone receptor-,and vimentin-negative. The cytological and surgical specimens showed a remarkable association of squamous metaplasia. Although cytopathological difficulties in determining malignancy of MDA endometrioid adenocarcinoma arising in the LUS are well-known, the following features worth noting include: 1) squamous metaplasia on cytological and histological slides; 2) epithelial cells incorporating polymorphic nuclear neutrophils on cytological slides; and 3) positive immunohistochemistry of p53 protein. Diagn. Cytopathol. 1999;21:117-121.

Persistent infection with human polyomavirus revealed by urinary cytology in a patient with heart transplantation. A case report.

BACKGROUND: Management after heart transplantation must deal with the twin risks of rejection and infection. Early infection with viral infection, particularly cytomegalovirus (CMV), is becoming more prevalent two to three months after transplantation. To our knowledge, there has been no previous report of human polyomavirus (HPOV) infection after heart transplantation. CASE: A 20-year-old male with a history of Kawasaki disease and who had suffered from severe congestive heart failure after a coronary artery bypass graft, underwent heart transplantation. Urinary cytology demonstrated HPOV infection, the diagnosis of which was established by the immunoperoxidase technique, in situ hybridization and electron microscopy. CONCLUSION: The definitive diagnosis of HPOV infection after a heart transplant can be made on urinary cytology.

Molecular cloning and expression of human ribonuclease 4 cDNA.

A cDNA coding for human ribonuclease 4 was isolated from a pancreas cDNA library and sequenced. This cDNA (996 bp) includes an entire open reading frame encoding mature protein (119 aa) following signal peptide (28 aa). Expression of mature protein in Escherichia coli showed an apparent molecular mass of about 16 kDa, which was slightly lower than the mature form of human RNase 1, in SDS-PAGE.

Ca2+-antagonistic effects of flurazepam, a benzodiazepine derivative, on isolated guinea-pig left atria.

Effects of flurazepam, a benzodiazepine derivative, on Ca2+-induced cardio-stimulant contractile activity in normal Tyrode's solution and Ca2+-mediated contraction in K+-rich (19-22 mM) Tyrode's solution were investigated in electrically driven left atrial preparations isolated from guinea-pigs. In normal Tyrode's solution, flurazepam (1 X 10(-6), 1 X 10(-5) and 1 X 10(-4) M) noncompetitively shifted the dose-response curves for CaCl2 downwards. In K+ (19 mM)-rich Tyrode's solution, flurazepam (3 X 10(-5) M) decreased contractile amplitude time-dependently; and after addition of CaCl2 (final: 8 mM), contractile amplitude was increased time-dependently. In K+ (19 mM)-depolarized preparations, flurazepam (3 X 10(-5) M) competitively shifted the dose-response curve for CaCl2 rightwards. In the K+ (22 mM)-depolarized isoproterenol (3.8 X 10(-6) M)-treated atrial preparation, flurazepam (3 X 10(-5) M) consistently suppressed contraction. Flurazepam (9 X 10(-5) M) suppressed atrial contraction in tetrodotoxin (TTX) (2 X 10(-5) M)-added normal Tyrode's solution, and CaCl2 (final: 8 mM) partially restored the contraction. These results suggest that flurazepam inhibits transmembrane Ca2+-influx into the atrial muscle cell.